Tuesday, 12 November 2013

Barking up the right tree

The happenstance discovery of quinine is reasonably well known, but with Cinchona pubescens flowering recently in Melbourne's Royal Botanic Gardens and my rediscovery of a picture I took a few years ago in the streets of Paris, it's time to tell it again.

It is said the treatment of malaria with quinine was the first successful use of a chemical compound to treat an infectious disease. Let's not debate whether the many herbal concoctions used to great effect for thousands of years predate the use of quinine, but simply reflect on the serendipity that led to less people succumbing to malaria.

From early in the seventeenth century the bark of the cinchona tree was used by Jesuit missionaries in South America to treat malaria, most probably borrowing from its use by the native people of the area.

No-one seems sure but it's possible a South American villager with high fever drank from a pool of stagnant water, noticing that it tasted quite bitter. The source of the bitterness was the surrounding quina-quina (as cinchona was called locally). However instead of being poisoned, as he feared, our villager began to recover. And so his village began to use this plant product to treat fever.

This story remains credible despite malaria not occurring in the Americas until the Europeans arrived and quina-quina not being mentioned in any of the early accounts of traditional remedies. Perhaps this happy event coincided with the arrival of the first Europeans or initially helped reduce a fever not related to malaria.

Another variation on the story is now considered to be untrue. In this one the Spanish Countess of Chinchon used the bark of the quina-quina to cure a fever she picked up in Peru, and then introduced the plant into Europe in 1638. True or not, the father of plant taxonomy, Carl Linnaeus, named the genus Cinchona after her.

No matter how it started, the bark took off as a malaria treatment and you can find samples in various museums of economic botany. Here is some in the Economic Botany Collection at Royal Botanic Gardens Kew, and you can find out much more about the history of cinchona on the same website.

Cinchona is one of more than 600 genera in the mostly tropical plant family Rubiaceae, also home to coffee (Coffea) and various other plants containing interesting and important chemicals. There are 23 species of Cinchona, all of which grow naturally in the Andes, and most of which contain at least some quinine. Cinchona pubescens has the most.

So what about this memorial (somewhere near the Jardin du Luxenbourg if I remember rightly) to Professeurs Pierre Pelletier and Joseph Conventou? In 1820 they were the first to extract and purify what they called quinine from the bark of Cinchona. Prior to their work the bark itself was dried, ground to a powder and then mixed directly into a liquid such as wine.

Quinine from cinchona remained the main malaria treatment for the next hundred years, until synthetic products (also from the '-quine' chemical family) proved to be even more effective. However in the late 1950s resistance began to develop in some forms of the malaria bug (Plasmodium falciparum). Quinine itself was reintroduced, particularly for severe cases, and it still remains part of the medical treatment of malaria.

Perhaps more interestingly (at least to an algal botherer - phycologist - such as myself) is that Plasmodium is a close relative of the dinoflagellate, a kind of alga best know for causing red tides and colouring up corals. Because of this relationship, the herbicide roundup can be used to kill Plasmodium cells. Roundup (glyphosate) disrupts chemical reactions within 'plastids', the package of photosynthetic apparati found in all algae and green plants, and there are vestigial plastids in Plasmodium. That's worth a statue, and the name Geoff McFadden from The University of Melbourne (a phycological colleague of mine and keen surfer as this picture from his website demonstrates) would be carved on at least one side.